Cerebral Cavernous Malformation (CCM) is a hereditary stroke syndrome that has no treatment other than neurosurgery. Loss of one of three genes causes CCM. By reducing the expression of one of these genes (CCM2) in the cells that line blood vessels (endothelial cells), unique structural and functional phenotypes result. We will use a chemical suppression screen in cell culture systems to discover small molecules that rescue these distinct phenotypes. Our high-throughput platform consists of two primary screens: the first is an imaging screen with machine-learning based phenotype analysis; the second screen uses electric cell substrate impedance sensing to detect changes in endothelial barrier function. We will then further screen the top candidate compounds in a mouse model of human CCM disease. The result of this project will be personalized medicine candidates for the treatment of CCM caused by mutations in the CCM2 gene.